Focal adhesion kinase (FAK) is a member of the non-receptor sub-family of protein tyrosine kinases and is expressed in various tissues and cell types. FAK acts as an early modulator in the integrin signalling cascade so that integrin clustering in response to various stimuli results in FAK autophosphorylation at Tyr397. This creates a motif that is recognised by various SH2 domain containing proteins, such as src. The FAK-src complex binds and phosphorylates many downstream molecules such as p130Cas, growth factor receptor bound protein-2 (Grb2) and phosphoinositide-3 kinase (PI3K) thereby transducing signals by many different, complex pathways which interact with each other1.
In normal cells FAK regulates various basic cellular functions such as proliferation and growth, protection from apoptosis, adhesion and cell spreading, invasion and migration. Elevated FAK expression, activity or signalling is associated with malignancy in a variety of cancer cells leading to promotion of cancer cell proliferation, increased invasion in vitro and an increase in metastases in vivo4.
Additionally FAK appears to be a key molecule in the activation of several signalling pathways initiated by angiogenic factors, including proliferation, migration and differentiation. Specific endothelial cell deletion of FAK revealed it to be crucial for vascular stability during vascular development3 
Therefore FAK may be useful in the treatment of pathological angiogensis, for example as an anti-angiogenic therapy in diseases such as cancer and retinopathy. FAK inhibitors may also have beneficial effects on the proliferation or invasive ability of tumour cells2. There is emerging evidence of a potential correlation between FAK expression with malignant transformation and therefore FAK inhibition could slow down disease progression.
International Patent Applications WO2008/115369, WO2008/073687, WO2007/072158, WO2007/0633848, WO2006/074057, WO2006/021457, WO2006/021454, WO2005/123191, WO2005/016894, WO2004/080980 and WO2001/64655 disclose compounds that are stated to have FAK inhibitory properties. The compound PF-00562271 is in early development as a FAK inhibitor for use in the treatment of cancer.
There is however a need to find further compounds that are FAK inhibitors, particularly compounds with appropriate pharmacokinetic and pharmacodynamic drug properties, and also that exhibit appropriate selectivity profile(s) against other kinases and receptors.    1. Chatzizacharias, N. A. et al. Expert Opin. Ther. Targets. 2007; 11(10):1315-1328    2. Angelucci, A et al. Current Pharmaceutical Design. 2007; 13:2129-2145    3. Braren, R. et al. JCB 2006; 1:151-162    4. Mitra, S K. Current opinion in Cell Biology 2006; 18:516-523    5. Chatzizacharias, N. A. et al. Histology Histopathol. 2008; 23: 629-650